The goal of the proposed research is to examine the neural correlates of depressive symptom reduction in individuals with major depressive disorder using functional magnetic resonance imaging (fMRI). Specifically, we propose to acquire functional imaging data from individuals with major depressive disorder at two points in time, both before and after an 8- to 15-week course of Brief Behavioral Activation Treatment for Depression, a structured and well-validated method of cognitive behavioral therapy designed to reduce sensitivity to loss and enhance sensitivity to reward (Hopko et al., 2003a). Imaging data will focus on activation of a reward network comprising the orbitofrontal and prefrontal cortices, the anterior cingulate, and, in particular, the ventral striatum, during anticipation of reward using the Wheel of Fortune Task, (Ernst et al., 2004). This previously validated task was designed to elicit responding to reward expectation and has been shown to activate this reward network in response to reward expectations in nonclinical samples (Ernst et al., 2005; Ernst et al., 2004). This reward network and the ventral striatum in particular, are critical for processing reward anticipation and cues of incentive motivation (e.g., Keedwell et al., 2005). Increased neural activation in this reward network in response to anticipation of reward after cognitive behavioral therapy will be evaluated in relation to symptom reduction in a number of domains, most notably symptoms of loss of pleasure (i.e., anhedonia). The proposed study has the potential to hone the targets of psychological interventions for major depressive disorder by identifying which components of therapy effect the anticipation of rewards, a central deficit in this psychiatric condition. The benefit to public health provided by this study would be a better understanding of how a specific form of psychotherapy may work to treat depression. The identification of brain markers of the effectiveness of a specific treatment for depression would enable future studies to evaluate a range of treatments, all with various costs and side-effect profiles, to determine optimum treatments for individuals suffering from major depressive disorder. Such a strategy is consistent with NIMH's mission to reduce the burden of psychiatric disorders. [unreadable] [unreadable] [unreadable]